组织驻留记忆T细胞在慢性肝病中的调控机制与治疗靶点

林金; 曾煜; 田展飞; 凡小丽

doi:10.12449/JCH250526

组织驻留记忆T细胞在慢性肝病中的调控机制与治疗靶点

DOI: 10.12449/JCH250526

四川大学华西医院消化系统肿瘤与肝病研究室，成都 610000

基金项目:

国家自然科学基金 (82100552);

四川大学-达州校市合作专项资金 (2022CDDZ-18)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：林金、曾煜撰写和修改论文，二者对本文贡献相同；田展飞绘制图表；凡小丽指导撰写文章并最后定稿。

详细信息

通信作者:
凡小丽， fanxiaoli@scu.edu.cn （ORCID： 0000-0002-8434-2969）

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出版历程
- 收稿日期: 2024-09-18
- 录用日期: 2024-10-22
- 出版日期: 2025-05-25

The regulatory role of tissue-resident memory T cells in chronic liver diseases and associated therapeutic targets

Laboratory of Gastrointestinal Cancer and Liver Disease，West China Hospital，Sichuan University，Chengdu 610000，China

Research funding:

National Natural Science Foundation of China (82100552);

Sichuan University-Dazhou Cooperation Fundation (2022CDDZ-18)

More Information

Corresponding author: FAN Xiaoli， fanxiaoli@scu.edu.cn （ORCID： 0000-0002-8434-2969）

摘要

摘要: 组织驻留记忆T细胞（T_RM细胞）是一类存在于组织中，具有组织特异性且不参与循环的记忆T细胞亚群。当潜在的危险攻击肝脏，如病原体（细菌或病毒等）侵袭或自身免疫反应过强时，T_RM细胞作为第一道免疫防线，在病毒性肝炎、自身免疫性肝病、代谢相关脂肪性肝病、肝硬化和肝移植中都发挥着重要作用。本文阐述了肝脏T_RM细胞的免疫表型，包括其表面标志物和转录谱，旨在进一步研究肝脏T_RM细胞在慢性肝病中的作用，并探索其作为免疫治疗靶点的潜在功能。
- 组织驻留记忆T细胞 /
- 肝疾病 /
- 免疫疗法
Abstract: Tissue-resident memory T cells （T_RM cells） are a subset of memory T cells that reside in tissues， exhibit tissue specificity， and do not recirculate. When potential hazards threaten the liver， such as pathogen invasion （bacteria， viruses， etc.） and excessive autoimmune responses， T_RM cells are essential as the first line of immune defense， playing an important role in viral hepatitis， autoimmune liver disease， metabolic dysfunction-associated fatty liver disease， liver cirrhosis， and liver transplantation. Here， we present the immunophenotypes of T_RM cells in the liver and their surface markers and transcriptional profiles， aiming to clarify the role of T_RM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.
- Tissue-resident Memory T Cells /
- Liver Diseases /
- Immunotherapy

HTML全文

注： IL-15R，白细胞介素15受体；IL-15，白细胞介素15； TGF-βR，转化生长因子β受体；TCR，T细胞抗原受体；MHCⅠ，主要组织相容性复合体Ⅰ类分子。

图 1 肝脏CD8⁺ T_RM细胞的表型和代谢特征

Figure 1. Phenotype and metabolic profiles of liver CD8⁺ T_RM cells

下载: 全尺寸图片幻灯片

注： a，病毒性肝炎中的肝脏T_RM细胞；b，MAFLD中的肝脏T_RM细胞；c，自身免疫性肝病中的肝脏T_RM细胞；d，肝硬化中的肝脏T_RM细胞。PANX1，泛连接蛋白1；CCL5，CC类趋化因子配体5；GzmB，颗粒酶B。

图 2 不同慢性肝病中的肝脏T_RM细胞

Figure 2. Hepatic T_RMcells in different chronic liver diseases create with biorender

下载: 全尺寸图片幻灯片

注： PRDM1，含PR域蛋白1；NR3C1，核受体亚家族3C组成员1；GR，糖皮质激素受体；TETs，10-11易位家族。

图 3 肝脏T_RM细胞作为免疫疗法的潜在靶点

Figure 3. Potential targets of hepatic TRM cells as immunotherapy

下载: 全尺寸图片幻灯片

表 1 T_RM细胞的一般特征

Table 1. General features of T_RM cells

项目	效应分子	功能
表面标志物	CD69	促进肝脏T_RM细胞的驻留状态并抑制S1PR1介导的细胞离开组织的过程
	CD103	与钙黏蛋白E的结合可能对T_RM细胞的定位、黏附和保留至关重要
	CD49a	通过与整合素β1结合形成异二聚体VLA-1，促进整合素β1与胶原蛋白Ⅳ结合，导致驻留细胞保留在上皮细胞
转录谱	BLIMP1、HOBIT	HOBIT和BLIMP1的共表达下调T_RM细胞中CCR7、KLF-2及S1PR1的表达，促进细胞驻留在组织中
	RUNX3	下调与循环T细胞发育相关的基因，并上调细胞驻留相关分子
	BHLHE40	诱导应激反应蛋白的表达，以促进应激下T_RM细胞的效应功能
	TBX21（T-bet）	有助于IL-15受体的表达，以实现T_RM细胞的长期存在
趋化因子		T_RM细胞的维持和效应功能已被证明需要持续的趋化因子刺激
趋化因子受体	CXCR3、CXCR6	通过结合单核细胞、肝窦内皮细胞和成纤维细胞分泌的多种趋化因子（如CXCL9、CXCL10、CXCL11和CXCL16），影响对T_RM细胞的保留和维持
注：BLIMP1，B细胞诱导成熟蛋白1；HOBIT，T细胞中BLIMP1的同源物；RUNX3，RUNT相关转录因子3；BHLHE40，E类基本螺旋环螺旋蛋白40；TBX21（T-bet），T盒转录因子21；CXCR，CXC趋化因子受体；CXCL，趋化因子CXC配体。

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